Impact of gender on response to immune checkpoint inhibitors in patients with non-small cell lung cancer undergoing second- or later-line treatment

BACKGROUND: Several previous clinical trials have reported that male patients with non-small cell lung cancer (NSCLC) respond better to immunotherapy than females. However, the impact of gender on prognosis remains uncertain because no real-world study considering various factors that affect patients’ response to immunotherapy with gender exists. Therefore, we evaluated the effect of gender on immunotherapy response adjusted by multiple factors in actual clinical practice. METHODS: This study was a single-center real-world retrospective cohort study, comprising 387 patients with NSCLC who received pembrolizumab, nivolumab, or atezolizumab alone as second- or later-line treatments. Subsequently, we compared their progression free survival (PFS) and overall survival (OS) scores based on gender, then analyzed prognostic factors accounting for immunotherapy response. RESULTS: The mean age of the understudied patients was 64.0 years old, comprising 68.7% males, with non-squamous cell carcinoma accounting for 70.3% of these patients. Male patients also showed higher smoking rates, programmed death-ligand 1 (PD-L1) expression, and expression of wild type epidermal growth factor receptor (EGFR), known as favorable prognostic factors. However, no difference in PFS and OS according to gender was observed [PFS 2.2 (male) vs. 2.1 (female) months, P=0.144; OS 7.6 (male) vs. 8.8 (female) months, P=0.383]. Furthermore, an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, high expression of PD-L1, and EGFR mutations were proposed as prognostic factors in multivariate analysis for PFS. Besides, ECOG performance status ≥2 and squamous cell carcinoma were poor prognostic factors accounting for OS. Yet, gender was not an independent prognostic factor in PFS and OS. CONCLUSIONS: Gender was not an independent prognostic factor for immunotherapy in real-world data although various factors affected immunotherapy response, such as wild type EGFR and high expression of PD-L1, which frequently occur in males.